Bixa orellana ethyl acetate fraction and its isolated compound ellagic acid attenuate the progression of MIA-induced osteoarthritis in rat knees.

Osteoarthritis (OA) is a pathology that is characterized by progressive erosion of articular cartilage. In this context, medicinal plants have become relevant tools regarding their potential role in the prevention and treatment of OA, being safe and effective. The aim of this work was investigate the therapeutic efficacy of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc) for the therapeutic treatment of OA induced by monosodium iodoacetate (MIA) in rats. The plant material was extracted via maceration with 70 % hydroalcoholic solvent (BoHE). The ethyl acetate (BoEA) fraction was by solvents in increasing order of polarity. The ElAc was identified and isolated in BoEA using high performance liquid chromatography (HPLC-DAD) and analytical curve. The OA was induced using MIA in the right knee at the knee joint. Doses of BoEA and ElAc were administered daily (every 24 h, orally) at concentrations of 50, 100 and 50 mg/kg, respectively, for 28 days after induced OA. We evaluated the animals through clinical and radiological examinations every 7 days and, on the 29th day, the animals were euthanized, the joints being removed for histopathological analysis and the serum for cytokine analysis. BoEA and ElAc compounds reduced inflammation and nociception in OA and were as effective as indomethacin in clinical parameters of joint discomfort and allodynia in rats, in addition to showing improvements in radiological and histopathological images, acting on the progress of cartilage deterioration, proving properties related to anti-inflammatory and analgesic processes, being important allies for new therapeutic interventions for the treatment of OA.

Evaluation of the In Vitro Wound-Healing Potential of Ayahuasca.

Ayahuasca is an Amazonian drink, which contains ß-carboline alkaloids and N,N-dimethyltryptamine. The aim of this study was to evaluate the healing potential of decoctions of a commercial mixture, four individual plants and four mixtures of two plants used in the ayahuasca preparation. Thus, the cytotoxic potential of the samples was evaluated and a wound-healing assay was performed with a NHDF cell line. Subsequently, a parallel artificial membrane permeability assay was also performed, to verify if any psychoactive compound could be absorbed by skin fibroblasts. The integrity and permeability of the cell layer were also evaluated, using the transepithelial electrical resistance assay and Lucifer yellow permeability assay, respectively. The compounds absorbed by the cell layer were quantified by high-performance liquid chromatography coupled to a diode array detector. The results showed that only one sample showed cytotoxicity and all the others promoted the migration of skin fibroblasts. Additionally, it was also verified that ß-carbolynic alkaloids and N,N-dimethyltriptamine were not absorbed by the cell layer, and in general, did not interfere with its permeability and integrity. To the best of our knowledge, this is the first study where ayahuasca's wound-healing potential was evaluated.

The Role of Herbal Medicine in the Treatment of Acne Vulgaris: A Systematic Review of Clinical Trials.

Over the past few decades, interest in medicinal plants and phytochemicals for the treatment of skin disorders, including acne vulgaris, has progressively increased. Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit, which mainly occurs in adolescents and young adults. The treatment focuses on the four main factors involved in its pathogenesis: increased sebum production, hyperkeratinization, overgrowth of Cutibacterium acnes, and inflammation. The treatment includes topical retinoids, benzoyl peroxide, antibiotics, and oral isotretinoin. In this regard, the use of herbal medicine as a complementary and alternative medicine is a promising strategy. The main objective of this study was to systematically evaluate the efficacy and safety of medicinal plants and phytochemicals in the treatment of acne vulgaris. Three scientific databases (PubMed, Web of Science, and Scopus) were searched from inception to January 2021. Clinical trials comparing herbal therapies with placebo or other medicines for the treatment of acne vulgaris were included and analyzed. Outcome measures of interest comprised acne lesions (inflammatory and noninflammatory), sebum production, acne severity, and quality of life. The risk of bias in the included randomized controlled trials (RCTs) was assessed using the Cochrane risk-of-bias tool. A total of 34 clinical trials involving 1753 participants met the inclusion criteria for this systematic review. Most trials showed that herbal medicine significantly reduces inflammatory and noninflammatory acne lesions and has a relevant effect on acne severity. Some medicinal plants revealed equal or higher efficacy to standard treatments. No significant difference between groups in sebum production and quality of life was observed and no severe adverse events were reported. This systematic review provides evidence that medicinal plants and phytochemicals are promising treatments for mild to moderate acne vulgaris. However, more quality of evidence and standardized methodologies are needed to support their effectiveness and safety claims.

Sweet Cherries as Anti-Cancer Agents: From Bioactive Compounds to Function.

Sweet cherries (Prunus avium L.) are among the most appreciated fruits worldwide because of their organoleptic properties and nutritional value. The accurate phytochemical composition and nutritional value of sweet cherries depends on the climatic region, cultivar, and bioaccessibility and bioavailability of specific compounds. Nevertheless, sweet cherry extracts are highly enriched in several phenolic compounds with relevant bioactivity. Over the years, technological advances in chemical analysis and fields as varied as proteomics, genomics and bioinformatics, have allowed the detailed characterization of the sweet cherry bioactive phytonutrients and their biological function. In this context, the effect of sweet cherries on suppressing important events in the carcinogenic process, such as oxidative stress and inflammation, was widely documented. Interestingly, results from our research group and others have widened the action of sweet cherries to many hallmarks of cancer, namely metabolic reprogramming. The present review discusses the anticarcinogenic potential of sweet cherries by addressing their phytochemical composition, the bioaccessibility and bioavailability of specific bioactive compounds, and the existing knowledge concerning the effects against oxidative stress, chronic inflammation, deregulated cell proliferation and apoptosis, invasion and metastization, and metabolic alterations. Globally, this review highlights the prospective use of sweet cherries as a dietary supplement or in cancer treatment.

Psychoactive Substances of Natural Origin: Toxicological Aspects, Therapeutic Properties and Analysis in Biological Samples.

The consumption of new psychoactive substances (NPSs) has been increasing, and this problem affects several countries worldwide. There is a class of NPSs of natural origin, consisting of plants and fungi, which have a wide range of alkaloids, responsible for causing relaxing, stimulating or hallucinogenic effects. The consumption of some of these substances is prompted by religious beliefs and cultural reasons, making the legislation very variable or even ambiguous. However, the abusive consumption of these substances can present an enormous risk to the health of the individuals, since their metabolism and effects are not yet fully known. Additionally, NPSs are widely spread over the internet, and their appearance is very fast, which requires the development of sophisticated analytical methodologies, capable of detecting these compounds. Thus, the objective of this work is to review the toxicological aspects, traditional use/therapeutic potential and the analytical methods developed in biological matrices in twelve plant specimens (Areca catechu, Argyreia nervosa, Ayahuasca, Catha edulis, Datura stramonium, Lophophora williamsii, Mandragora officinarum, Mitragyna speciosa, Piper methysticum Forst, Psilocybe, Salvia divinorum and Tabernanthe iboga).

Phytochemical Characterization, Bioactivities Evaluation and Synergistic Effect of Arbutus unedo and Crataegus monogyna Extracts with Amphotericin B.

The increased resistance to drugs by pathogens is a serious problem, with plants showing to be promising sources for the development of new drugs or the improvement of the effect of existing antimicrobial agents. Considering this, we aimed to evaluate the bioactivities of Arbutus unedo and Crataegus monogyna. Thus, the leaves were first extracted with methanol and then fractionated with different solvents. Phenolic compound profiles were assessed by HPLC-PDA-MSn and the antioxidant activity was evaluated using DPPH method and ß-carotene bleaching assay. The antimicrobial activity of extracts was tested against several microorganisms. A. unedo contained mainly galloyl esters, hydrolysable tannins, and flavonoids, while in C. monogyna, 5-caffeoylquinic acid and flavonoids were the most representative polyphenols. Crude extracts showed antioxidant activity and the extracts and fractions displayed a weak antibacterial activity; however inhibiting the growth of Candida tropicalis and C. lusitaniae to which A. unedo extract showed higher activity. Most of the extracts and fractions demonstrated synergistic or additive interactions with amphotericin B against Candida spp. Therefore, the present study revealed significant bioactive properties of the extracts and fractions of A. unedo and C. monogyna, such as antioxidant and antifungal activities.

Julbernardia paniculata and Pterocarpus angolensis: From Ethnobotanical Surveys to Phytochemical Characterization and Bioactivities Evaluation.

Julbernardia paniculata and Pterocarpus angolensis are two plant species with important application in African traditional medicine, particularly in Angola, in the treatment of several diseases. However, scientific studies concerning these species are scarce. The goal of this work was to know better which medicinal approaches are used by the Huíla population in Angola by means of ethnobotanical surveys. Furthermore, extracts of both plants were phytochemically characterized. Antioxidant, anti-inflammatory, wound-healing activities, and potential cytotoxicity were also studied. With this study it was possible to verify that 67% of the individuals that use medicinal plants are women, and their main therapeutic uses are the treatment of problems of the digestive system and skin disorders. Barks of J. paniculata and leaves of P. angolensis are the most often used plant parts. Through high-performance liquid chromatography coupled to diode-array detector (HPLC-DAD) and GC-MS it was possible to characterize the chemical composition of the two species, which are rich in phenolic compounds, terpenes, terpenoids, sesquiterpenoids and fatty acids. Both plants showed to possess antioxidant, anti-inflammatory proprieties, and wound-healing activity. To the best of our knowledge, this is the most comprehensive study of these two species and the first ethnobotanical and ethnopharmacological study of medicinal plants from this region of Angola.

Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspects, and Analytical Determination.

Although the medicinal properties of Cannabis species have been known for centuries, the interest on its main active secondary metabolites as therapeutic alternatives for several pathologies has grown in recent years. This potential use has been a revolution worldwide concerning public health, production, use and sale of cannabis, and has led inclusively to legislation changes in some countries. The scientific advances and concerns of the scientific community have allowed a better understanding of cannabis derivatives as pharmacological options in several conditions, such as appetite stimulation, pain treatment, skin pathologies, anticonvulsant therapy, neurodegenerative diseases, and infectious diseases. However, there is some controversy regarding the legal and ethical implications of their use and routes of administration, also concerning the adverse health consequences and deaths attributed to marijuana consumption, and these represent some of the complexities associated with the use of these compounds as therapeutic drugs. This review comprehends the main secondary metabolites of Cannabis, approaching their therapeutic potential and applications, as well as their potential risks, in order to differentiate the consumption as recreational drugs. There will be also a focus on the analytical methodologies for their analysis, in order to aid health professionals and toxicologists in cases where these compounds are present.

Mitragyna speciosa: Clinical, Toxicological Aspects and Analysis in Biological and Non-Biological Samples.

The abuse of psychotropic substances is a well-known phenomenon, and many of them are usually associated with ancestral traditions and home remedies. This is the case of Mitragyna speciosa (kratom), a tropical tree used to improve work performance and to withstand great heat. According to several published studies, the main reasons for kratom consumption involve improving sexual performance and endurance, but also social and recreational uses for the feeling of happiness and euphoria; it is also used for medical purposes as a pain reliever, and in the treatment of diarrhea, fever, diabetes, and hypertension. However, this plant has gained more popularity amongst young people over the last years. Since it is available on the internet for purchase, its use is now widely as a drug of abuse, namely as a new psychoactive substance, being a cheaper alternative to opioids that does not require medical prescription in most countries. According to internet surveys by the European Monitoring Centre for Drugs and Drug Addiction in 2008 and 2011, kratom was one of the most widely supplied new psychoactive substances. The composition of kratom is complex; in fact, more than 40 different alkaloids have been identified in Mitragyna speciosa so far, the major constituent being mitragynine, which is exclusive to this plant. Besides mitragynine, alkaloids such as corynantheidine and 7-hydroxamitragynine also present pharmacological effects, a feature that may be attributed to the remaining constituents as well. The main goal of this review is not only to understand the origin, chemistry, consumption, and analytical methodologies for analysis and mechanism of action, but also the use of secondary metabolites of kratom as therapeutic drugs and the assessment of potential risks associated with its consumption, in order to aid health professionals, toxicologists, and police authorities in cases where this plant is present.

Metabolic changes after licorice consumption: A systematic review with meta-analysis and trial sequential analysis of clinical trials.

BACKGROUND: Licorice, also known as liquorice, refers to the root of Glycyrrhiza glabra L., a product widely available in the market in the form of licorice flavonoid oil (LFO), which is a concentrate of licorice flavonoids, being a dietary ingredient for functional foods with potential benefits for overweight subjects. PURPOSE: To summarize the results of the numerous clinical trials, and to clarify the metabolic changes after licorice consumption, through a systematic review with meta-analysis and Trial Sequential Analysis (TSA) of clinical trials. METHODS: This review was designed according to the PRISMA (Preferred Reported Items for Systematic Reviews and Meta-Analysis) recommendations. Several electronic databases were searched to identify the clinical trials. A meta-analysis approach was then developed to statistically analyze the results, followed by TSA and meta-regression analyses. RESULTS: A total 26 clinical trials were considered for the quantitative synthesis of the data, totalizing 985 patients enrolled. Overall, it was possible to verify that the licorice consumption significantly reduces the body weight (WMD: -0.433 kg; 95% CI: -0.683 to -0.183; p-value = 0.001) and consequently the body mass index (BMI) of patients (WMD: -0.150 kg/m2; 95% CI: -0.241 to -0.058; p-value = 0.001). Another result with statistical significance was the increase in the diastolic blood pressure (DBP) (1.737 mmHg; 95% CI: 0.835 to 2.621; p-value < 0.0001) observed for the group subjected to licorice consumption, which is related to the hypernatremia also caused by licorice. CONCLUSION: The present meta-analysis demonstrated the positive effects of licorice consumption on the reduction of body weight and BMI of patients. However, the results also show the increase in blood pressure of patients associated with the hypernatremia caused by licorice. Consequently, licorice consumption should be avoided by hypertensive patients.

Differing energy densities with laser 670nm InGaP controls inflammation and collagen reorganization in burns.

PURPOSE: This study compared different energy densities of laser on second degrees burns in rats aiming to determine the most effective dosimetry in stimulation of the healing process. METHODS: Burns were induced in the dorsal skin of 54 animals divided into three groups (n: 18): 1-without treatment; 2-irradiated lesions by the Indium Gallium Phosphide (InGaP) 670nm (4.93J/cm2) laser; 3-irradiated lesions by the InGaP-670nm (9.86J/cm2) laser. Samples were collected on the 2, 10 and 18 days after injury for structural, morphometry, biochemical analysis and Western blotting. RESULTS: The energy densities examined were effective in significantly increasing the total number of fibroblasts and blood vessels and reduce the number of inflammatory cells particularly in irradiated lesions with 9.86J/cm2. This same energy density significantly increased the amount of GAGs (Glycosaminoglycans), decreased the TGF-ß1 (Transforming Growth Factor ß1) and increased the VEGF (Vascular and Endothelial Growth Factor) during the experimental period. This energy density also significantly increased the Collagen type I and decreased Collagen type III and the active isoform of metalloproteinase 9 (MMP-9). CONCLUSIONS: The energy density of 9.86J/cm2 was more effective in promoting cellular responses related to neoangiogenesis, decreasing inflammation and collagen fibers reorganization.

Can Cranberries Contribute to Reduce the Incidence of Urinary Tract Infections? A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Clinical Trials.

PURPOSE: We sought to clarify the association between cranberry intake and the prevention of urinary tract infections. MATERIALS AND METHODS: This systematic review, which complies with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement, was done as a meta-analysis and trial sequential analysis of clinical trials. RESULTS: The findings clearly showed the potential use of cranberries for the clinical condition of urinary tract infection. Cranberry products significantly reduced the incidence of urinary tract infections as indicated by the weighted risk ratio (0.6750, 95% CI 0.5516-0.7965, p <0.0001). The results of subgroup analysis demonstrated that patients at some risk for urinary tract infections were more susceptible to the effects of cranberry ingestion. CONCLUSIONS: The results of the current study could be used by physicians to recommend cranberry ingestion to decrease the incidence of urinary tract infections, particularly in individuals with recurrent urinary tract infections. This would also reduce the administration of antibiotics, which could be beneficial since antibiotics can lead to the worldwide emergence of antibiotic resistant microorganisms.

Biological Properties of Plant-Derived Alkylresorcinols: Mini-Review.

Alkylresorcinols are compounds which belong to the family of phenolic lipids, and are usually found in numerous biological species. In the particular case of higher plants, alkylresorcinols have been found in various counterparts with chains of thirteen to twenty-seven carbon atoms containing several saturations. Due to the demonstrated antimicrobial properties of many naturally occurring members of the alkylresorcinols family, it is possible to conclude that these compounds act as defensive agents in plants. Previous studies led to the isolation and identification of 5-alkylresorcinols that cleave DNA. Additionally, in the literature, there are several other biological effects attributed to some resorcinol derivatives, namely, cytotoxic, anticarcinogenic, antiproliferative, antileishmanial and antioxidant properties. This mini-review intends to outline the biological activities of the most relevant alkylresorcinols isolated from plants and to propose future directions for subsequent studies regarding the effective biological effects of this class of compounds.

Stumps of Eucalyptus globulus as a source of antioxidant and antimicrobial polyphenols.

These past years have seen an enormous development of the area of natural antioxidants and antimicrobials. Eucalyptus globulus is widely cultivated in subtropical and Mediterranean regions in intensive short rotation coppice plantations. In the Portuguese context, E. globulus is the third species in terms of forest area. The stump is the basal part of the tree, including the near-the-ground stem portion and the woody roots that remain after stem felling. The purpose of this work was to study the phytochemical profile and to evaluate the antioxidant and antimicrobial properties of several crude stump wood and stump bark extracts of E. globulus, comparing it with similar extracts of E. globulus wood (industrial chips). The results showed the presence of high concentrations of total phenolic compounds (>200 mg GAE/g extract) and flavonoids (>10 mg QE/g extract) in E. globulus stump extracts. Generally the stump wood extracts stands out from the other ones, presenting the highest percentages of inhibition of linoleic acid oxidation. It was also possible to conclude that the extracts were more active against Gram-positive bacteria, presenting low MIC values. This study thus provides information supporting the economic valorization of E. globulus stump wood.

An alkenylresorcinol derivative from Hakea sericea fruits and their antimicrobial activity.

Hakea sericea has been introduced to Portugal for ornamental purposes. The phytochemical composition and the antioxidant, antibacterial, antibiofilm and cytotoxic properties of this shrub species have been previously reported. The present work describes the bioassay-guided fractionation of the crude methanolic extract of H. sericea fruits and the isolation of 9-(3,5-dihydroxy-4-methylphenyl)nona-3(Z)-enoic acid. The structure of this new compound was established by one- and two-dimensional NMR and IR spectroscopy, and high-resolution mass spectrometry. The antibacterial properties of the new alkenylresorcinolwere studied by determining its MIC values against several strains of Gram-positive and Gram-negative bacteria using the resazurin microtiter assay. The new alkenylresorcinol inhibited the growth of Enterococcus faecalis, Listeria monocytogenes and Bacillus cereus with MIC values of 0.31, 0.02 and 0.16 mg/mL, respectively. Good MIC values were obtained against Staphylococcus aureus strains (0.005 - 0.16 mg/mL), including the clinical isolates (SA 01/10, SA 02/10 and SA 03/10) and MRSA strains.

Bioactive compounds, RP-HPLC analysis of phenolics, and antioxidant activity of some Portuguese shrub species extracts.

In the ecosystem of Serra Da Estrela, some plant species have the potential to be used as raw material for extraction of bioactive products. The goal of this work was to determine the phenolic, flavonoid, tannin and alkaloid contents of the methanolic extracts of some shrubs (Echinospartum ibericum, Pterospartum tridentatum, Juniperus communis, Ruscus aculeatus, Rubus ulmifolius, Hakea sericea, Cytisus multiflorus, Crataegus monogyna, Erica arborea and Ipomoea acuminata), and then to correlate the phenolic compounds and flavonoids with the antioxidant activity of each extract. The Folin-Ciocalteu's method was used for the determination of total phenols, and tannins were then precipitated with polyvinylpolypyrrolidone (PVPP); a colorimetric method with aluminum chloride was used for the determination of flavonoids, and a Dragendorff's reagent method was used for total alkaloid estimation. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and beta-carotene bleaching tests were used to assess the antioxidant activity of extracts. The identification of phenolic compounds present in extracts was performed using RP-HPLC. A positive linear correlation between antioxidant activity index and total phenolic content of methanolic extracts was observed. The RP-HPLC procedure showed that the most common compounds were ferulic and ellagic acids and quercetin. Most of the studied shrubs have significant antioxidant properties that are probably due to the existence of phenolic compounds in the extracts. It is noteworthy to emphasize that for Echinospartum ibericum, Hakea sericea and Ipomoea acuminata, to the best of our knowledge, no phytochemical studies have been undertaken nor their use in traditional medicine been described.